Key result
Partial α-adrenergic blockade reduces resting sympathetic transduction while maintaining pressor responses to apnea.
Why the study?
It was unclear whether blunted sympathetic transduction to blood pressure at high altitude is driven by reduced adrenergic communication or other factors such as augmented dilatory signaling.
Does partial α-adrenergic blockade alter resting systemic sympathetic transduction and pressor responses to sympathoexcitation in acclimatizing lowlanders and Andean highlanders at high altitude?
Does partial α-adrenergic blockade alter resting systemic sympathetic transduction and pressor responses to sympathoexcitation in acclimatizing lowlanders and Andean highlanders at high altitude?
p-value: p=<0.001
Resting blood pressure control at high altitude is modulated primarily through α-adrenergic receptors in both lowlanders and highlanders, but pressor responses to stress may rely on alternative mechanisms.
α-adrenergic receptors mediate sympathetic transduction at altitude; leaves open alternative pressor mechanisms and requires prospective validation.
Elevated muscle sympathetic nerve activity (MSNA) at high altitude is associated with blunted transduction of sympathetic signals to blood pressure in lowlanders and indigenous Andean highlanders. However, it is unclear whether this is due to reduced adrenergic communication or other factors (e.g. augmented dilatory signaling). Therefore, we quantified the contribution of α-adrenoreceptor activity to 1) resting systemic sympathetic transduction and 2) pressor responses to sympathoexcitation in acclimatizing lowlanders (9M, 4F) and Andean highlanders (15M) at 4,300m. MSNA (microneurography) and mean arterial pressure (MAP; finger photoplethysmography) were measured at rest, during maximal voluntary apnea, and with an α 1 -adrenergic agonist (phenylephrine) prior to and following partial α-adrenergic blockade (phentolamine). Sympathetic transduction was quantified as the slope of the relationship between MAP and total MSNA associated with sequences of sympathetic bursts. Transduction was attenuated in both lowlanders (0.0041±0.0037 to 0.0017±0.0017mmHg∙% -1 , P=0.026) and highlanders (0.0033±0.0024 to 0.0008±0.0007mmHg∙% -1 , P=0.005) under α-adrenergic blockade (main effect P<0.001) and was not different between groups (main effect P=0.276). However, pressor responses to apnea (lowlanders, +25±5mmHg; highlanders, +22±7mmHg) were unchanged following phentolamine (lowlanders, +25±8mmHg; highlanders, +20±8mmHg; main effect P=0.174) despite unchanged MSNA responses between conditions (main effect P=0.162). Highlanders exhibited reduced MSNA responses compared to lowlanders regardless of condition (main effect P=0.014). Partial α-adrenergic blockade reduced sympathetic transduction similarly in both groups. Yet, apnea responsiveness was maintained, achieved through lesser sympathoexcitation in highlanders. This suggests that resting blood pressure control is modulated primarily through α-adrenergic receptors in both populations, but pressor responses to stress may result from alternative mechanisms.
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Berg et al. (2026) studied High altitude acclimatization (n=28). Partial α-adrenergic blockade (phentolamine) vs. Baseline (prior to blockade) was evaluated on Resting systemic sympathetic transduction (p=<0.001). Partial α-adrenergic blockade reduced resting sympathetic transduction in both lowlanders and highlanders (main effect P<0.001), while pressor responses to apnea were maintained.
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